Features include always present findings: Profound intellectual disability and Global developmental delay; and common findings: Flexion contracture, Myoclonic seizure, Hypertelorism, and Axial hypotonia and others. 43 total HPO annotations.

GAD1 encodes glutamate decarboxylase 1 (594 aa). Catalyzes the synthesis of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) with pyridoxal 5'-phosphate as cofactor Highest expression in Brain Frontal Cortex BA9 (58.7 TPM) and Brain Anterior cingulate cortex BA24 (48.9 TPM).

Developmental and epileptic encephalopathy 89 is associated with mutations in the GAD1 gene on chromosome 2.

The GAD1 protein participates in GAD1 gene expression is stimulated by MECP2, PXLP-K405-GAD1 decarboxylates L-Glu to form GABA, and MECP2 regulates transcription of genes involved in GABA signaling pathways.

GAD1 is classified as a druggable target (Druggable Genome and Enzyme categories) with score 0.0.

Genetic testing for GAD1 is available. Testing is considered confirmatory for diagnosis.

Phenotype severity distribution: 2 always present features, 10 common features.

No clinical trials have been registered for developmental and epileptic encephalopathy 89.

4 publications have been identified in PubMed for developmental and epileptic encephalopathy 89. Research spans Basic Science / Preclinical (50%), Epidemiology / Natural History (25%), and Gene Therapy / Novel Therapeutics (25%).

Recent Publications

• Chen C (2025). [PMID: 39847501](https://pubmed.ncbi.nlm.nih.gov/39847501/). *J Clin Invest*. [Gene Therapy / Novel Therapeutics]

• Lai D (2025). [PMID: 40418734](https://pubmed.ncbi.nlm.nih.gov/40418734/). *Brain*. [Basic Science / Preclinical]

• Lichtarge J (2024). [PMID: 39872998](https://pubmed.ncbi.nlm.nih.gov/39872998/). *Front Neurosci*. [Epidemiology / Natural History]

• Lai D (2024). [PMID: 39763953](https://pubmed.ncbi.nlm.nih.gov/39763953/). *bioRxiv*. [Basic Science / Preclinical]